2-mercapto, alkyl, acetyl and furfuryl-sulfide pyrazines

ABSTRACT

Disclosed is a group of compounds which has been found to be useful in the area of flavor-note alteration. The compounds have the following formula: ##STR1## wherein n, R 1  and R 2  are as defined below.

This is a division of application Ser. No. 482,819 filed June 24, 2974now United States Pat. No. 4,038,435 which is a division of applicationSer. No. 243,866 filed Apr. 13, 1972 and now abandoned which is adivision of application Ser. No. 70,560 filed Sept. 8, 1970 now U.S.Pat. No. 3,702,253; which latter application is a continuation ofnow-abandoned application Ser. No. 543,069 filed Apr. 18, 1966, which isa continuation-in-part of now-abandoned application Ser. No. 452,342filed Apr. 30, 1965.

The invention relates to flavor agents in general. More particularly theinvention relates to chemical compounds or compositions which have beenfound to have utility in the alteration of flavor or flavorcharacteristics of substances, whether naturally occurring or synthetic.Still more particularly the invention relates to a group of chemicalcompounds which have been found to be useful in the area of flavor-notealteration, whether by the enhancement of flavors or flavor-notes thatare characteristic in a substance, by the alteration of a flavor or aflavor-note from a less to a more desirable one, or by the complete orpartial masking of a flavor or flavor-note.

As is generally recognized by those familiar with the art, the scienceof flavor technology is an extremely complex one. Although much is knownabout flavor and flavor technology there is still a great deal to belearned in the field and the body of scientific literature is beingrapidly expanded by those working in the area. The technology of flavorsynthesis and blending of various flavor elements to achieve certaindesirable results is of great commercial importance at the present stageof industrial advance. Commercial production of consumer goods fromsynthetic starting materials is becoming more and more common, anddesirable, as world population continues to increase its demands uponthe finite capacity for the production of natural products. Industry isalso continually seeking means of upgrading natural products -- methodsof altering or enhancing the qualities of taste of less desirablenatural products -- usually more abundant -- into more desirable productqualities. Often, for example, a product can be made commerciallyattractive only by masking or blanking out an undesirable flavorcomponent. Formerly, before the advent of the flavor chemist and histechnology, this unit of production would have been lost, or at least,would have had to have been re-processed to a useable quality. By theuse of specifically designed flavoring agents, however, the undesirableflavor note can be eliminated or masked with another desirable one, andthe expensive and time-consuming re-processing step eliminated or theproduction batch saved for use. Too, it is common in some segments ofthe industry, particularly the food industry, to add flavor agents toproduction units to enhance or bring out a desirable flavorcharacteristics of products -- and by so doing to render the productmore desirable from a consumer preference standpoint.

It is the object of this invention therefore, to provide the flavortechnologist with additional tools for his use in the alteration of foodflavors, whether it be flavor or flavor-note alteration generally or theenhancement or improvement of flavor or flavor notes specifically.

It is a further object of the invention to furnish a group of chemicalcompositions which have utility in the technology of flavor alteration,whether added to solid or liquid compositions for human consumption, andwhich may be used in either solid or liquid form.

A further object of the invention is to describe a group of chemicalcompounds having desirable utility as flavor agents which may beprepared synthetically, thus enabling the food technologist to alter orenhance his product without drawing upon a natural product for theflavor agent.

A still further object of the invention is to describe a group ofchemical compounds capable of synthesis from readily available organicsubstances which may be used singly or in combination to alter theflavor or flavor notes of compositions for food use, whether used inmicro-quantities such as parts-per-million or in larger quantities, asthe dictates of the end results may require.

Other objects will become apparent to those skilled in the art as thedescription proceeds.

Thus, in accordance with the concept of the instant invention, there isset out below a group of compounds which have been found to have utilityas flavor agents and to represent valuable materials to the foodtechnologist who wishes to alter the flavor components of foods or foodproducts either liquid foods or beverages, such as fruit and vegetablejuices, milk, coffee, tea, cocoa, chocolate, and the like or solid foodssuch as cereals, flours, confections, vegetables, meats, etc. The flavoragents may be used either in liquid or solid form and are used inquantities designed to give the desired results, as will be more clearlyexplained as the description proceeds.

The chemical compounds which have been found to have utility as flavoragents may be generally classified as pyrazine sulfur compounds.

The flavor agents or flavor modifying compositions of this invention areavailable to the food technologists in a variety of forms. It is usuallypreferable to use the agents in the form of a solution, for ease ofdilution, exactitude of measurement, efficiency of distribution in theend use, etc. However the chemical nature of the compound, itssolubility in acceptable solvents, its stability, and othercharacteristics may dictate the form in which it is used.

The amounts of the agents used is also subject to wide variation, ofcourse. More concentrated materials, and those with the greatest degreeof flavor modifying ability will be used in lesser amounts. Some degreeof experimentation is, of course, required to achieve the desiredresults. A small, but flavor modifying amount, of the agents is blendedwith the material whose total flavor is to be altered, the amountdepending upon the end result desired.

Two different types of methods were used in testing the compounds listedin this specification for their utility as flavor agents, flavormodifiers, flavor alteration agents, flavor-note enhancers, and thelike. The first type method (A) served the purpose of determining theintrinsic taste, flavor and aroma of each individual compound. Thesecond type methods (B) and (C) were used for testing the flavor- andaroma-modifying or -enhancing effects of the compounds hereinafterlisted on coffee products and more particularly on spray-dried solublecoffee products commercially known as "instant coffee".

Method A.

The vehicle used for testing the flavor compounds was a 65% solution ofcane sugar in tap water. The flavor compounds were incorporated in thissugar syrup in the form of 1% or 1 per 1000 by weight solutions in 96%ethyl alcohol. The concentration of the flavor compounds in the sugarsyrup varied between about 0.005 and 5 g. for 100 liters of syrupaccording to the varying strength of flavor compounds. Samples of eachflavored sugar syrup were submitted to the members of the tastingpanels. After tasting the samples each member had to give an evaluationof each flavor compound in terms of descriptive words.

In the evaluation of materials for the alteration or enhancement ofcoffee flavor or of coffee flavor notes it is essential that theequipment used, coffee pots, cups, spoons, measuring equipment, etc. beabsolutely clean prior to use.

Method B.

The coffee base was prepared by dissolving 1 g. of a commercialspray-dried soluble coffee in boiling water. A sufficient number of potswas prepared to provide one pot for each flavor agent to be evaluatedplus one control. The flavor agent was added to the coffee base in theform of a 1% or 1 per 1000 by weight alcoholic solution atconcentrations varying between 0.005 and 5 g. of flavor agent for 100liters of coffee base. The measured quantity of the flavor agent wasadded to a pot of the coffee base material, stirred well, and pouredimmediately into cups for the organoleptic evaluation. The taste testswere made within a short time (not more than 15 minutes) after the finalcomposition to be tested was prepared.

The organoleptic evaluation involved grading a series of cups that werecoded, the taster merely rating the coded cups against the standard orcontrol which did not contain the flavor agent. The standard was placedat the first position in a series of cups. The tasters were asked toascertain whether or not there existed differences in the flavor of thesamples to be tested as compared with the control. The tasters werefurthermore asked to describe and characterize the various flavor notesand types determined.

Method C.

Using boiling Crystal Spring Water, to provide a clean starting taste, a1.35% solution of relatively bland tasting commercially availablespray-dried soluble coffee was prepared. The containers used -preferably the lower portion of a glass coffee maker - was absolutelyclean, as was the other equipment used, e.g. cups and spoons.

A sufficient number of containers, or pots, were used to accomodate eachflavor fraction to be studied, plus one control. The flavor fraction wasmeasured carefully with a micro-syringe, adding from 2 to 150microliters of the flavor fraction per pot. The mixture of coffeesolution and flavor fraction was stirred and immediately poured intocups for tasting. At least 5 experienced tasters are used. The tastingshould begin at least within 15 minutes after the solution is prepared.If not, the solution should be discarded and fresh solution prepared.

The cups are coded and the samples are not identified. A standard sampleis included in which no flavor fraction has been added. The taster isasked to identify and describe the flavor enhancement or modificationnoted.

In the following specific description of the pyrazine sulfur compoundsthere is first given the structural formula followed by a list ofmembers of the group which have been found to have outstanding utilityin the concept of this invention. Immediately following the chemicalname of each member there is given the commercial source or a literaturereference giving a method for its preparation. Commercially availableproducts will be identified by the abbreviation c.a., and may beobtained from FLUKA, A.G., Buchs S.G., Switzerland; ALDRICH CHEM. CO.,Milwaukee, Wis.; DR. F. RASCHIG GMBH, Ludwigshafen a. Rh., West-Germany;or K & K LABORATORIES INC., Plainview, NY. 11803.

In those instances wherein new compounds are described a detailed methodof preparation is given following the list of the group members. Newcompounds will be identified by the abbreviation n.c.

The results of the organoleptic evaluation tests are set out in thetable following the detailed description of the group of compounds.

I - Pyrazine Sulfur Compounds

The compounds of this group can be represented by the following generalformulae: ##STR2## wherein n is 0, 1 or 2, R₁ represents hydrogen,methyl, ethyl or furfuryl and R₂ stands for hydrogen or methyl with theproviso that R₁ and R₂ cannot both be methyl if n is 0;

Illustrative examples of compounds corresponding to formula (1) include:

(1) a. (2-methylpyrazinyl-3, -5 and -6) furfuryl sulfide n.c.

b. pyrazinylmethyl-mercaptan n.c.

c. pyrazinylmethyl methyl sulfide n.c.

d. pyrazinylmethyl ethyl sulfide n.c.

e. pyrazinylmethyl furfuryl sulfide n.c.

f. pyrazinylmethylthiol acetate n.c.

g. 2-pyrazinyl-ethyl mercaptan n.c.

h. 2-pyrazinyl-ethyl methyl sulfide n.c.

i. 2-pyrazinyl-ethyl ethyl sulfide n.c.

j. 2-pyrazinyl-ethyl furfuryl sulfide n.c.

k. 2-pyrazinyl-ethylthiol acetate n.c.

(1) a. (2-Methylpyrazinyl-3, -5 and -6) furfuryl sulfide (mixture): Amixture of 2-methyl-3-, 5- and 6-chloropyrazine was prepared bychlorination of 2-methylpyrazine according to the method described in J.Org. Chem. 26, 2356, 2360 (1961). 0.2 Mole of the above2-methyl-chloropyrazine mixture was added to 0.2 mole of a sodiumfurfurylmercaptide suspension in 250 ml. of xylene. The mixture wasboiled for 6 hours. After cooling 250 ml. of water were added, theorganic layer was concentrated and distilled. 13.5 g. of a mixture of(2-methylpyrazinyl-3, -5 and-6) furfuryl sulfide were obtained; b.p.153°-156° C./10 Torr; n_(D) ²⁰ = 1.5970; d₄ ²⁰ = 1.2164.

(1) b. Pyrazinylmethylmercaptan: a solution of 6.3 g. (0.05 mole) ofchloromethylpyrazine [obtained according to the method described in J.Org. Chem. 26, 2356 (1961)] in 20 ml. of ether was added slowly, withstirring, to a solution of sodium hydrogensulfide (60%) in 50 ml. ofabsolute methanol. Stirring of the reaction mixture at room temperaturewas continued for 3 hours. The precipitate which had formed was removedby filtering, the solvents were evaporated, and the residue wasdissolved in water. The solution was extracted twice with ether. Theaqueous phase was neutralized with acetic acid and extracted with ether.After drying of the extract the solvent was evaporated and the residuedistilled. 0.25 g. of pyrazinylmethylmercaptan boiling at 44°-45°C./0.07 mm. Hg. was obtained.

(1) c. Pyrazinylmethyl methyl sulfide was prepared according to themethod described in Houben-Weyl, 4th ed., vol. 9, 97 (1955) by reactingchloromethylpyrazine [obtained by the method described in J. Org. Chem.26, 2356 (1961)] with sodium methylmercaptide. The product has a b.p. of105°-106° C./12 mm. Hg.

(1) d. Pyrazinylmethyl ethyl sulfide was prepared by thesame method asused for compound (1) c., except that sodium ethylmercaptide was used inplace of sodium methylmercaptide. The product has a b.p. of 114°-116°C./12 mm. Hg.

(1) e. Pyrazinylmethyl furfuryl sulfide was prepared by the same methodas used for compound (1) c., except that sodium furfurylmercaptide wasused instead of sodium methylmercaptide. The product has a b.p. of 116°C./0.05 mm. Hg.

(1) f. Pyrazinylmethylthiol acetate was prepared by acetylation ofpyrazinylmethylthiol according to the method described in Houben-Weyl,4th. ed., vol. 9, 753 (1955). The product has a b.p. of 52° C./0.02 mm.Hg.

(1) g. 2-Pyrazinyl-ethyl mercaptan was prepared by reactingvinylpyrazine [obtained by the method described in J. Org. Chem. 27,1363 (1962)] and hydrolizing the resulting thiolic acid ester accordingto the method described in J. Org. Chem. 22, 980 (1957). The product hasa b.p. of 56.5°-60° C./0.003 mm. Hg.

(1) h. 2-Pyrazinyl-ethyl methyl sulfide was prepared by reactingvinylpyrazine [c.f. J. Org. Chem. 27, 1363 (1962] with methylmercaptanby the action of ultra violet light and in the presence of benzoylperoxide by the method described in Acta Chem. Scand. 8,, 295 (1954).The product was identified by mass spectrometry. It has a b.p. of57°-69° C. at 0.05 mm. Hg.

(1) i. 2-Pyrazinyl-ethyl ethyl sulfide was prepared by the method usedfor compound (1) h., but using ethylmercaptan. It has a b.p. of 75°C./0.03 mm. Hg.

(1) j. 2-Pyrazinyl-ethyl furfuryl sulfide was prepared by the methodused for compound (1) h., but using furfuralmercaptan. The product has ab.p. of 116°-117° C./0.01 mm. Hg.

(1) k. 2-Pyrazinyl-ethylthiol acetate was prepared by reactingvinylpyrazine with thioacetic acid in the presence of benzoyl peroxideas a catalyst according to the method described in J. Org. Chem. 27,2853 (1962). The product has a b.p. of 80° C./0.02 mm. Hg.

                  TABLE I                                                         ______________________________________                                        Number  Test    Quantity  Organoleptic Characterization                       ______________________________________                                        (1)a.   A       0.1       roasted coffee-like taste                           (1)a.   B       0.1       roasted, coffee grounds note                        (1)b.   A       2.0       roasted meat-like taste                             (1)c.   A       0.1       cabbage taste                                       (1)c.   B       0.01-0.02 strawy, dark flavor note                            (1)d.   A       0.02-0.3  cabbage, onion taste                                (1)e.   A       2.0       coffee-like taste                                   (1)e.   C       0.135     sulfury, toasted, nutty, burnt                                                cereal note                                         (2)a.   A       1.0       coffee-like taste                                   ______________________________________                                    

As has been stated above the compounds having utility in the concept ofthis invention may be added to substances in varying amounts to alter orto modify the flavor of the substance by masking or blanking outundesirable flavors, by enhancing or fortifying desirable flavor orflavor notes, or by adding to the original substance an entirely new anddifferent flavor. As will also be apparent to those skilled in the artvarious mixtures or blends of the flavor agents described may be used toachieve a desired flavor or flavor note. If, for example, one wishes toenhance a certain flavor note, or group of flavor notes present in asubstance such as coffee, one needs only mix together certain of thedescribed flavor agents to obtain the desired result.

It should be kept in mind, as will be appreciated by thoseskilled-in-the-art, that with many flavors it is possible to imitate thenatural flavor by selecting a limited number of the flavor enhancingsubstances examplified above. Coffee aroma, on the other hand, is muchmore complex than the ordinary flavoring materials and may necessitatethe combination of many more of the examplified ingredients forreproduction.

It will also be understood that whereas the preferred embodiment of thisinvention is directed toward the enhancement or modification of coffeeflavors, the concept of the invention has much wider application. Whilesome of the compounds may be characterized by terms which are notdirectly related to coffee flavors, these compounds, when used in morecomplex formulae, may contribute desirable flavor notes to the overallflavor and aroma.

To summarize briefly this invention relates to a group of chemicalcompounds which have been found to have utility for the alteration ormodification of the flavor of other materials. These compounds, calledflavor agents or flavor modifiers, may be used in minute quantities toenhance the natural flavor of substances to which they are added, or toalter or modify a flavor which is undesirable, or to impart to asubstance additional or different flavors or flavor notes. The flavoragents of the invention are used in minor, but flavor altering amounts,in any case, in quantities sufficient to obtain the desired results. Theflavor modifiers are of particular importance and usefulness in themodification, alteration or enhancement of the flavor of coffeebeverages made from soluble coffee and the preferred embodiment of theinvention contemplates their use in conjunction with such products.

The flavor agents of the invention may be added at a convenient step inthe soluble coffee process such as plating the dried soluble coffee witha desired dilution of the flavor agent in an acceptable solutionfollowed by drying. In certain instances the desired agent may be addeddirectly to a concentrated coffee extract and the mixture dried into asoluble coffee product which contains the flavor agent as an integralpart thereof. Other methods of incorporation of the agents will suggestthemselves to those skilled in the art and may, of course, be usedwithout departing from the inventive concept, which may be described asbeing a composition of matter comprising a combination of a solublecoffee product, however prepared, whether liquid or solid, concentratedor dilute, which contains combined therewith a minor, but flavormodifying amount, of a flavor agent as described herein.

What is claimed is:
 1. A compound of the formula ##STR3## wherein n is0, 1 or 2, R₁ is hydrogen, methyl, ethyl, acetyl or furfuryl and R₂ ishydrogen or methyl with the proviso that R₁ and R₂ cannot both be methylif n is
 0. 2. The compound of claim 1 wherein the pyrazine sulfurcompound is pyrazinylmethyl-mercaptan.
 3. The compound of claim 1wherein the pyrazine sulfur compound is pyrazinylmethyl methyl sulfide.4. The compound of claim 1 wherein the pyrazine sulfur compound ispyrazinylmethyl ethyl sulfide.
 5. The compound of claim 1 wherein thepyrazine sulfur compound is pyrazinylmethyl furfuryl sulfide.
 6. Thecompound of claim 1 wherein the pyrazine sulfur compound ispyrazinylmethylthiol acetate.
 7. The compound of claim 1 wherein thepyrazine sulfur compound is 2-pyrazinyl-ethyl mercaptan.
 8. The compoundof claim 1 wherein the pyrazine sulfur compound is 2-pyrazinyl-methylsulfide.
 9. The compound of claim 1 wherein the pyrazine sulfur compoundis 2-pyrazinyl-ethyl ethyl sulfide.
 10. The compound of claim 1 whereinthe pyrazine sulfur compound is 2-pyrazinyl-ethyl furfuryl sulfide. 11.The compound of claim 1 wherein the pyrazine sulfur compound is2-pyrazinyl-ethylthiol acetate.